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Drug fends off kidney cancer progression

New data from an international, multicenter Phase III clinical trial has observed that the experimental targeted treatment everolimus (RAD001) significantly delays cancer progression in patients with metastatic kidney cancer whose disease had worsened on other therapys. The study was led by Robert Motzer, MD, an attending doctor at Memorial Sloan-Kettering Cancer Center (MSKCC), who will present the findings on May 31 at the annual meeting of the American Society for Clinical Oncology.

 

This study has given us a new and clearly useful tool for treating renal cell tumors, and everolimus is an important step forward in terms of disease management and quality of life for patients living with this disease, said Dr. Motzer.

Kidney cancer is among the ten most common cancers in both men and women. The American Cancer Society estimates that there will be about 54,390 new cases of kidney cancer diagnosed in the US in 2008, and that about 13,010 people will die from the disease.

Everolimus, a once-daily oral treatment, targets the mTOR protein, which acts as a central regulator of tumor cell division, cell metabolism, and blood vessel growth. It is currently being reviewed for the therapy of several other cancers including lymphoma and neuroendocrine tumors.

More than 400 patients participated in this study, all of whom had disease that had progressed with currently available targeted therapies sunitinib and/or sorafenib. Patients were randomized to receive everolimus or placebo. After six months, 26 percent of patients in the everolimus group had disease that had not progressed, in comparison to only 2 percent of the placebo group. The average difference in progression free survival was four months for everolimus, in comparison to 1.9 months for the placebo group.

In February, 2008, an independent monitoring committee stopped the Phase III trial after interim results were positive and allowed scientists to offer everolimus to the patients receiving placebo.

For almost 20 years, we made no headway in the management of advanced kidney cancer, notes Dr. Motzer. Recently, the identification of several new angiogenesis- targeted agents has provided us with new therapy options and an improved outlook for patients with advanced kidney cancer. Based on the results of this trial, everolimus could become another tool in our armamentarium and, in the future, kidney cancer is likely to be managed as a chronic disease with these types of therapy advances.

Everolimus was well tolerated by patients and the most common side effects were mouth ulcers, anemia, skin rash and weakness.…

Cancer risk higher for women in discontinued hormone treatment trial

A follow up study of participants in the Womens Health Initiative (WHI) clinical trial led by a University of North Carolina at Chapel Hill researcher has observed that women who were taking the combined hormone treatment of estrogen plus progestin may have an increased risk of cancer since the intervention was stopped, in comparison to participants in the trials placebo group.

However, the increased risks of heart disease, stroke and blood clots which had been seen in women taking the treatment as part of the WHI trial have diminished in the three years since scientists stopped it, as per a research studyreported in the March 5 issue of the Journal of the American Medical Association.

The studys lead author is Dr. Gerardo Heiss, a Kenan professor of epidemiology in the UNC School of Public Health.

The WHI trial of estrogen plus progestin which included 16,608 healthy postmenopausal women was originally designed to study what effect the hormone therapy would have on cardiovascular disease, cancer risks and bone fractures.

The trial was stopped in July 2002 after participants had been on the treatment for an average of 5.6 years because scientists saw an increased risk of breast cancer and cardiovascular disease in women randomly assigned to hormone treatment, compared with those who received a placebo.

Since then, Heiss and other WHI scientists at collaborating institutions have examined the risks and benefits experienced by 15,730 trial participants who had follow-up visits from July 2002 to March 2005, after they stopped hormone treatment.

Scientists have observed that the yearly event rates for the outcome all cancer was higher for the estrogen plus progestin group (1.56 percent per year [n = 281]) than the placebo group (1.26 percent per year [n = 218]). This reflects a greater risk of invasive breast cancer and other cancers in the estrogen plus progestin group. Eventhough the risk of breast cancer remained elevated during the follow-up, the risk was less than that experienced towards the end of the trial period.

The WHI researchers did not expect to find an increased overall risk of cancer after stopping the estrogen plus progestin, Heiss said. The increased risk is small, but the follow up did indicate there are higher levels of breast cancer, lung cancer, stroke and death among those who had taken this treatment. Thus, there is a need for prevention efforts through healthy lifestyle choices, risk factor control and regular screening activities as recommended by health care practitioners. This is good advice for everyone though, whether they have taken estrogen plus progestin for 3.5 to 8.5 years as in this study or not.

A summary of the risks and benefits (called the global index) included outcomes for coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture and death due to other causes. The scientists observed that this measure was 12 percent higher in women randomly assigned to receive estrogen plus progestin compared with the placebo, and did not visibly change after the intervention was stopped.

The rates of colorectal cancer did not differ significantly between the two groups and rates of endometrial cancer were lower in the estrogen plus progestin group.

The risk of cardiovascular events was comparable between the two groups in the follow up assessment, Heiss said, meaning that the increased risks seen in women assigned to estrogen plus progestin during the trial period weakened after the study drugs were stopped.

The risk of fractures during the postintervention follow-up was similar among women in both groups for each type of fracture considered: hip, vertebral and other osteoporotic fractures.

The follow-up after stopping estrogen plus progestin use confirms the trials main conclusion that combination hormone treatment should not be used to prevent disease in healthy, postmenopausal women, Heiss said. The most important message to women who have stopped this hormone treatment is the need for continued prevention and screening activities through their physicians, for all important preventable conditions.…